Causes of dna damage

How does DNA damage cause apoptosis? What are the types of DNA damage? Hydrolysis: DNA consists of long strands of sugar molecules called deoxyribose that are linked together by phosphate groups. Each sugar molecule carries one of the four natural DNA bases: adenine, guanine, cytosine, or thymine (A, G, C, or T).

Damage to DNA that occurs naturally can result from metabolic or hydrolytic processes.

Metabolism releases compounds that damage DNA including reactive oxygen species , reactive nitrogen species , reactive carbonyl species , lipid peroxidation products and alkylating agents , among others , while hydrolysis cleaves chemical bonds in DNA. During these chemical reactions, the mutagenic effects of ionizing radiations are produce causing chromosome breaks and irregularities in the DNA. Oxidative damage is one cause of DNA damage. Non-ionizing radiation, like ultraviolet radiation, have longer wavelengths and carry much lower energy. They are hence, less penetrative, unlike X-rays.

DNA damage may also result from exposure to polycyclic aromatic hydrocarbons (PAHs ). PAHs are potent, ubiquitous atmospheric pollutants commonly associated with oil, coal, cigarette smoke, and automobile exhaust fumes.

A common marker for DNA damage due to PAHs is Benzo (a) pyrene diol epoxide (BPDE). Damage to cellular DNA is involved in mutagenesis and the development of cancer. The DNA in a human cell undergoes several thousand to a million damaging events per day, generated by both external (exogenous) and internal metabolic (endogenous) processes. Genomic mutations can also be carried over into daughter generations of cells if the mutation is not repaired prior to mitosis.

Once cells lose their ability to effectively repair damaged DNA , there are three possible responses (see Figure 1). The cell may become senescent, i. See full list on sigmaaldrich. For many years, exogenous sources of damage have been thought to be the primary cause of DNA mutations leading to cancer. However, Jackson and Loeb proposed that endogenous sources of DNA damage also contribute significantly to mutations that lead to malignancy.

Both environmental and cellular sources can result in similar types of DNA damage. DNA can be attacked by physical and chemical mutagens. UV radiation produces covalent bonds that crosslink adjacent pyrimidine (cytosine and thymine) bases in the DNA strand.

Ionizing radiation (X-rays) initiates DNA mutations by generating free radicals within the cell that create reactive oxygen species (ROS) and result in single-strand and double-strand breaks in the double helix. While the cell is able to evolve into either an apoptotic or senescent state, these actions are performed as a last resort. For each type of DNA damage, the cell has evolved a specific method of repairing the damage or eliminating the damaging compound.

The reaction is not a catalytic (enzymatic) reaction but is stoichiometric (chemical), consuming one molecule of MGMT for each adduct removed. Cells that have been engineered to overexpress MGMT are more resistant to cancer, likely because they are able to negate a larger amount of alkylating damage. A recent study by Niture, et al. DNA polymerases such as polymerase-δ contain proofreading activities and are primarily involved in replication error repair.

When an error is detec. Base excision repair (BER) involves multiple enzymes to excise and replace a single damaged nucleotide base. The base modifications primarily repaired by BER enzymes are those damaged by endogenous oxidation and hydrolysis.

A DNA glycosylase cleaves the bond between the nucleotide base and ribose, leaving the ribose phosphate chain of the DNA intact but resulting in an apurinic or apyrimidinic (AP) site. Oxoguanine DNA glycosylase I (Ogg1) removes 8-dihydro-8-oxoguanine (8-oxoG), one of the base mutations generated by reactive oxygen species. Polymorphism in the human OGGgene is associated with the risk of various cancers such as lung and prostate cancer. N-Methylpurine DNA glycosylase (MPG) is able to remove a variety of modified purine bases.

The AP sites in the DNA that result from the action of BER enzymes, as. Double-strand breaks in DNA can result in loss and rearrangement of genomic sequences. These breaks are repaired by either nonhomologous end-joining (NHEJ) or by homologous recombination (HR), also called recombinational repair or template–assisted repair. This mechanism requires the presence of an identical or nearly identical sequence linked to the damaged DNA region via the centromere for use as a repair template.

Non-homologous end-joining (NHEJ) is used at other points of the cell cycle when sister chromatids are not available for use as HR templates. While DNA damage is a key factor in the development and evolution of cancer cells, continued damage is used as part of clinical treatments for cancer, forcing malignant cells into apoptosis or senescence. Many chemotheraputic drugs such as bleomycin, mitomycin, and cisplatin, are effective because they cause further DNA damage in cancer cells that replicate at a faster rate than surrounding tissue. In order to block this survival mechanism within cancer cells, clinical trials are now being performed using inhibitors to specific DNA repair enzymes, including MGMT, PARP, and DNA -PK.

In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in as many as million individual molecular lesions per cell per day. But survival rates are improving for many types of cancer, thanks to improvements in cancer screening and cancer treatment. Signs and symptoms caused by cancer will vary depending on what part of the body is affected. Some general signs and symptoms associated with, but not specific to, cancer, include: 1. Lump or area of thickening that can be felt under the skin 3. Weight changes, including unintended loss or gain 4. Persistent cough or trouble.

Changes in bowel or bladder habits 6. The DNA inside a cell is packaged into a large number of individual genes, each of which contains a set of instructions telling the cell what functions to perform, as well as how to grow and divide. Errors in the instructions can cause the cell to stop its normal function and may allow a cell to become cancerous. Pain can be caused by cancer or by cancer treatment, though not all cancer is painful. Medications and other approaches can effectively treat cancer-related pain.

Fatigue in people with cancer has many causes , but it can often be managed. Difficulty breathing. There's no certain way to prevent cancer.

But doctors have identified several ways of reducing your cancer risk, such as: 1. If you don't smoke, don't start. Smoking is linked to several types of cancer — not just lung cancer. Cancer or cancer treatment may caus. Stopping now will reduce your risk of cancer in the future. Avoid excessive sun exposure.

Harmful ultraviolet (UV) rays from the sun can increase your risk of skin cancer. Limit your sun exposure by staying in the shade, wearing prot. DNA damage can also result from endogenous metabolic and biochemical reactions, some of which are not well understood. Hydrolysis reactions can partially or completely cleave the nucleotide base from the DNA strand.

Sequencing studies on DNA extracted from very old samples, termed ancient DNA , have determined that this is the major damage complicating data analysis (8). Cytosine deamination, like AP site formation, is caused by hydrolysis and is probably present in the DNA extracted from many sources. A plethora of factors can cause sperm DNA damage , including protamine imbalances, abortive apoptosis, advanced male age, oxidative stress, storage temperatures, and infections , while sperm DNA. Such damages may then be repaired or, if unrepaire trigger cell death.

Our study found that the smoke toxin left its distinctive. These effects are mainly due to adduct formation with DNA , RNA and protein. In addition, it also causes lipid peroxidation as well as oxidative damage to DNA.

AFBpossess genotoxic potential in a variety of test systems. Over time, chronic inflammation can cause DNA damage and lead to cancer. For example, people with chronic inflammatory bowel diseases, such as ulcerative colitis and Crohn disease, have an increased risk of colon cancer. A number of forces can cause gene mutations, such as smoking, radiation, viruses, cancer-causing chemicals (carcinogens), obesity, hormones, chronic inflammation and a lack of exercise. Gene mutations occur frequently during normal cell growth.

However, cells contain a mechanism that recognizes when a mistake occurs and repairs the mistake.